Studies are directed toward detection of the cases for decline in immunity with aging, with the initial approach being to determine whether the handling of an antigen changes as an animal ages. NIA colony Fischer-344 rats are the experimental model for all aging studies; however, Sprague-Dawley rats were used to develop techniques and to obtain preliminary data. Antigen localization was quantitated in various tissues of colony rats of 6, 12, 18 and 24 months of age following intravenous injection of 3H-BSA (tritiated aniline-azo-bovine serum albumin). The finding of decreased antigen in the liver with aging has confirmed the feasibility of the in-depth study of this tissue, which previous study had established to be a major tissue for antigen handling and for transfer of immunity via hepatocytes and polysomes that contained co-isolated antigen. Accordingly, investigations that determined changes at the tissue level in the colony rats are being extended to define the responsible cellular and subcellular changes. Intrinsic and extrinsic factors in aging, relative to the compartmentalization of antigen, are being investigated by transfer of cells (e.g. hepatocytes) and organelles (e.g. liver polysomes) from aged immunized to young unimmunized rats and from young immunized to aged rats. In vitro reactions of cells of the liver and lymphoid tissue are being studied to reveal how an immune response matures and declines with aging.